A combination of light flashes and sound waves at a frequency of 40 hertz stimulates the removal of toxic amyloid protein fragments from the brains of lab mice with symptoms similar to Alzheimer’s disease. The stimulation causes the fluid that cleans the brain to flow faster. The authors speak of a possible new mechanism by which the washing of amyloid from the brain can be enhanced. The study, led by brain researcher Li-Huei Tsai of the Massachusetts Institute of Technology in the United States, was published in the scientific journal Nature.
In previous studies, Tsai and her colleagues saw that this 40 Hz stimulation reduced the accumulation of amyloid in various parts of the cerebral cortex, such as the visual and auditory cortex, and in the hippocampus, the memory area. In the new study they investigated how this happened.
Genetically modified mice
The stimulation appears to influence brain waves, the collective rhythm in which large groups of brain cells fire. Brain waves vary in frequency: there are fast waves, which occur during relaxation or concentration, and slower ones, which occur during deep sleep. The frequency of 40 Hz stimulates the fastest brain waves, gamma waves. These occur during demanding cognitive activities such as studying and problem solving. And people with Alzheimer’s disease often have fewer gamma waves.
The increased gamma waves stimulate the flow in the mice in the ‘sewage system’ in the brain, the glymphatic system. This is a system of spaces around the blood vessels in the brain in which cerebrospinal fluid flows and which removes harmful waste products.
“It is interesting that these researchers come up with a mechanistic explanation,” responds Niels Prins, neurologist and director of the Brain Research Center, which conducts research into Alzheimer’s medications. “We indeed see changes in the gamma waves in people with Alzheimer’s and other forms of dementia.”
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In the genetically modified mice in the study, large amounts of amyloid accumulate in the brain, just like in Alzheimer’s. The researchers exposed these mice in their cages to light that flickered at a frequency of 40 Hz. At the same time, 40 Hz sound was heard, a low humming sound. As a control, there were also mice in which light and sound sounded with various other frequencies.
Glymphatic system
Only the 40 Hz stimulation accelerated the exchange of clean and ‘dirty’ cerebrospinal fluid and dilated the draining lymphatic vessels. In addition, certain brain cells produced more vasointestinal peptide (VIP) after stimulation, a small protein that also influences blood flow.
The positive effect on amyloid flushing by the audiovisual stimulation disappeared when the researchers chemically blocked the fluid exchange, and also when they inhibited the production of VIP. This shows that the stimulation activates the flow and drainage of the glymphatic system.
Whether the effect of stimulation on amyloid will also be seen in people with Alzheimer’s, and whether this affects the disease, remains to be seen. “Most of what we know about the glymphatic system has been discovered and described in laboratory animals, the number of studies in humans is still limited,” says geriatric psychiatrist Maarten Van Den Bossche. “But there are more and more indications that this system works in a similar way in humans.” At KU Leuven in Belgium, Van Den Bossche is researching ways to use sound stimuli to… slow brain waves to promote deep sleep in people with dementiain the hope that waste will be better disposed of.
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Gamma stimulation with sound or light is already attracting a lot of interest as a treatment for neurodegenerative disorders. The therapy has been studied in small studies in people with Alzheimer’s disease for a few years. Tsai herself also does this, in her spin-off company CognitoTherapeutics.
“There are many indications that the glymphatic system also plays a role in other neurodegenerative disorders,” says Van Den Bossche. “This study reveals a new mechanism through which new types of treatments may be developed. But there is still a long way to go before it is clear whether this also plays a role in people with dementia.”